An understanding of the mechanisms that underlie primary palate development is necessary for further progress to be made in research related to malformations such as cleft lip and palate. From our past studies we have determined that an orderly, sequential pattern of decline in rates of cell proliferation produces region-specific differences in growth rates throughout the primarly palate of the avian embryo. This pattern of decline was closely associated with the appearance of subpopulations of cells which exit from rapidly proliferating pools and which appeared to be quiescent. Recent studies suggest that quiescent and/or slow cycling cells were ultimately found in chondrogenic regions and that these cells undergo a cell cycle block prior to overt chondrogenesis. Correlative studies of cell communication revealed that the distribution of gap junctions was non-random and that the highest concentrations were found in the subepithelial mesenchyme of the maxillary process. These data, when integrated with our cell cycle data for the same regions, suggest that relationships exist between patterns of cell communication, the pattern of change in cell cycle kinetics, and epithelial-mesenchymal interaction. Future efforts will be directed toward determining (1) the extent to which epithelial-mesenchymal interaction is necessary for the induction or maintenance of patterns of cell communication, (2) whether epithelial-mesenchymal interaction is necessary for the maintenance of cell proliferation rates in subjacent mesenchyme, (3) what sequential, and potentially causal, relationships exist between alterations in epithelial-mesenchymal interaction, changes in the pattern of cell communication and the maintenance of cell proliferation rates, and (4) to determine the effect of uncoupling of cell communication on cell cycle progression. Fluorescence immunocytochemistry, transmission electron microscopy, autoradiography, organ culture, and tissue recombination techniques will be employed. Microinjection of individual cells with antibody to the 27,000 dalton gap junctional protein will be used to block cell communication. The findings from this project will be extended in other studies for analysis of the pathogenesis of malformations in mammalian embryos.